Dr. Susan Greenspan is proposed, by the Research Core Advisory Committee, for support in the Harvard GRTC for career consolidation. Her project "The Coenzyme PQQ, in Age-related Dopamine Regulation" represents a special opportunity to extend Dr. Greenspan's research on neuroendocrine regulatory mechanisms in normal aging. Dr. Greenspan is a trained Endocrinologist, currently a 4th year trainee in the Division of Aging Physician Scientist Training Program who has recently received the Nathan Shock Award from the Biological Sciences Section of the Gerontological Society of America, as a promising new investigator. The studies proposed by Dr. Greenspan will be conducted over a two year period and provide pilot data from which to generate support for her first independent funding. The hypotheses to be tested include 1) that the age-related physiologic decline in dopamine-B-hydroxylase activity results from decreases or alterations in pyrroloquinoline quinone (PQQ) metabolism or transport; 2) that pathologic states of dopamine deficiency reflect further losses of PQQ content, alterations in binding to carrier protein or the apoenzyme; and 3) that the mechanism of PQQ decline results from alterations in PQQ supply, biosynthesis, metabolism or transport. The specific studies will be conducted under the mentorship of Dr. Paul Gallop, an established investigator in Gerontology who has a solid track record in the development of metabolically skilled researchers. The Research Cores of the GRTC that will support these studies include the RIA Core, the Subject Recruitment Core and the Biostatistical Cores.